Ulrike M. Lorenz
- Diploma, Freie University, Berlin
- PhD, Freie University/Max-Planck-Institut, Berlin
- Associate Professor, Microbiology, Immunology, and Cancer Biology
- Phone: 434-243-2623
- Email: email@example.com
- Website: http://www.virginia.edu/microbiology/Lorenz-Lab/
Involvement of the protein tyrosine phosphatase SHP-1 in signal transduction pathways
Tyrosyl phosphorylation and dephosphorylation of proteins are a key regulatory mechanism in many normal signal transduction pathways leading to cell proliferation, differentiation, and death. The steady state level of tyrosyl phosphorylation on any protein is determined by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). While a lot is known about the structure and functions of PTKs, relatively little is known about the details of PTPs' participation in signal transduction.
My research interest focuses on the involvement of the PTP SHP-1 in the above described processes. SHP-1 is a non-transmembrane, src homology 2 (SH2)-domain containing PTP expressed primarily in hematopoietic cells of all lineages and at lower levels in epithelial cells. In hematopoietic cells, SHP-1 has been found to be a negative regulator of a variety of receptors. Mutations in the SHP1 gene have been shown to cause the motheaten (me/me) phenotype. Mice homozygous for the me allele display a panoply of hematopoietic disorders resulting in death two to three weeks after birth. The research presently ongoing in my lab can be divided into two major projects: (a) the role of SHP-1 in T cell development and function and (b) the role of SHP-1 in the development of breast tumors.
In order to address the question how SHP1 is involved in various signal transduction pathways, my laboratory employs techniques of protein chemistry, molecular biology and cell biology along with genetic approaches using me/me mice. Our goal is to understand the biological function(s) of SHP1 and their underlying mechanism(s) using a combination of in vitro and in vivo approaches.
- Mercadante E, Lorenz U. Breaking Free of Control: How Conventional T Cells Overcome Regulatory T Cell Suppression. Frontiers in immunology. 2016;7 193. PMID: 27242798 | PMCID: PMC4870238
- Walsh J, Zheng J, Smirnov I, Lorenz U, Tung K, Kipnis J. Regulatory T cells in central nervous system injury: a double-edged sword. Journal of immunology (Baltimore, Md. : 1950). 2014;193(10): 5013-22. PMID: 25320276 | PMCID: PMC4225170
- Mauldin I, Tung K, Lorenz U. The tyrosine phosphatase SHP-1 dampens murine Th17 development. Blood. 2012;119(19): 4419-29. PMID: 22438258 | PMCID: PMC3362360
- Protein tyrosine phosphatase assays. Current protocols in immunology / edited by John E. Coligan ... [et al.]. 2011; Unit 11.7. PMID: 21462163 | PMCID: PMC3097125
- Iype T, Sankarshanan M, Mauldin I, Mullins D, Lorenz U. The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells. Journal of immunology (Baltimore, Md. : 1950). 2010;185(10): 6115-27. PMID: 20952680 | PMCID: PMC2974050
- SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunological reviews. 2009;228(1): 342-59. PMID: 19290938 | PMCID: PMC2669678
- Ravichandran K, Lorenz U. Engulfment of apoptotic cells: signals for a good meal. Nature reviews. Immunology. 2007;7(12): 964-74. PMID: 18037898
- Sankarshanan M, Ma Z, Iype T, Lorenz U. Identification of a novel lipid raft-targeting motif in Src homology 2-containing phosphatase 1. Journal of immunology (Baltimore, Md. : 1950). 2007;179(1): 483-90. PMID: 17579069